Phosphabicyclononane-containing Ru complexes: Efficient pre-catalysts for olefin metathesis reactions

Article abstract of DOI:10.1021/jo702169p

(Chemical Equation Presented) The catalytic performances of three Phosphabicyclononane (Phoban)-containing ruthenium-based pre-catalysts have been evaluated for metathesis transformations. A wide screening of substrates in ring-closing metathesis reactions reveals the greater efficiency of pre-catalyst 4. Comparison of the catalytic activities of 4 with Grubbs' first-generation pre-catalyst illustrates the key role of the Phoban ligand. Additionally, a comparative study of three Phoban-containing pre-catalysts has been conducted for the self-metathesis of 1-octene at low catalyst loading (25-100 ppm).

Full text of DOI:10.1021/jo702169p

Phosphabicyclononane-Containing Ru Complexes: Efficient
Pre-Catalysts for Olefin Metathesis Reactions
†
†
‡
‡
Fabien Boeda, Herv e´ Clavier, Margaritha Jordaan, Wolfgang H. Meyer, and
,
†
Steven P. Nolan*
Institute of Chemical Research of Catalonia (ICIQ), AV. Pa ¨ı sos Catalans, 16, 43007 Tarragona, Spain,
and Sasol Technology (Pty), Ltd., R&D DiVision, 1 Klasie HaVenga Road, Sasolburg, 1947, South Africa
snolan@iciq.es
ReceiVed October 6, 2007
The catalytic performances of three Phosphabicyclononane (Phoban)-containing ruthenium-based pre-
catalysts have been evaluated for metathesis transformations. A wide screening of substrates in ring-
closing metathesis reactions reveals the greater efficiency of pre-catalyst 4. Comparison of the catalytic
activities of 4 with Grubbs’ first-generation pre-catalyst illustrates the key role of the Phoban ligand.
Additionally, a comparative study of three Phoban-containing pre-catalysts has been conducted for the
self-metathesis of 1-octene at low catalyst loading (25-100 ppm).
2
Introduction
considerable attention over the past decade. Subsequent to the
3
discovery by Grubbs of catalyst 1a in 1995, the replacement
of a tricyclohexylphosphine ligand by a N-heterocyclic carbene
(NHC) led to analogues 1b,c and allowed for an improved
stabilization of the active species. Following this groundbreaking
Olefin metathesis represents a powerful tool in modern
synthetic chemistry. Remarkably, its range of applications spans
4
1
from ring-closing metathesis (RCM) and cross metathesis (CM)
to ring-opening metathesis polymerization (ROMP) and acyclic
diene metathesis polymerization (ADMET). Because ruthenium-
based complexes are recognized as efficient catalysts and are
tolerant to various functionalities, they have been the focus of
(2) For reviews on Ru-based metathesis catalysts, see: (a) Trnka, T. M.;
Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18-29. (b) Handbook of
Metathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weinheim, Germany 2003;
pp 1-204. (c) Schrock, R. R.; Hoveyda, A. H. Angew. Chem., Int. Ed.
2
003, 42, 4592-4633. (d) Astruc, D. New J. Chem. 2005, 29, 42-56. (e)
Colacino, E.; Martinez, J.; Lamaty, F. Coord. Chem. ReV. 2007, 251, 726-
7
64. (f) Beligny, S.; Blechert, S. In N-Heterocyclic Carbenes in Synthesis;
†
ICIQ.
Nolan, S. P., Ed.; Wiley-VCH: Weinheim, Germany, 2006; pp 1-25. (g)
Despagnet-Ayoub, E.; Ritter, T. In N-Heterocyclic Carbenes in Transition
Metal Catalysis; Glorius, F., Ed.; Springer-Verlag: Berlin/Heidelberg,
Germany, 2007; pp 193-218.
(3) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 2039-2041.
(4) (a) Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am.
Chem. Soc. 1999, 121, 2674-2678. (b) Scholl, M.; Trnka, T. M.; Morgan,
J. P.; Grubbs, R. H. Tetrahedron Lett. 1999, 40, 2247-2250. (c) Scholl,
M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953-956.
‡
Sasol Technology R&D affiliation.
(
1) (a) Connon, S. J.; Blechert, S. Angew. Chem., Int. Ed. 2003, 42,
1
900-1923. (b) Donohoe, T. J.; Orr, A. J.; Bingham, M. Angew. Chem.,
Int. Ed. 2006, 45, 2664-2670. (c) Nicolaou, K. C.; Bulger, P. G.; Sarlah,
D. Angew. Chem., Int. Ed. 2005, 44, 4490-4527. (d) Deiters, A.; Martin,
S. F. Chem. ReV. 2004, 104, 2199-2238. (e) Villar, H.; Frings, M.; Bolm,
C. Chem. Soc. ReV. 2007, 36, 55-66. (f) Compain, P. AdV. Synth. Catal.
2
2
007, 349, 1829-1846. (g) Holub, N.; Blechert, S. Chem. Asian J. 2007,
, 1064-1082.
1
0.1021/jo702169p CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/06/2007
J. Org. Chem. 2008, 73, 259-263
259

Boeda et al.
FIGURE 1. Representative Ru-based metathesis pre-catalysts.
FIGURE 2. Structures of Phoban-containing pre-catalysts.
modification, further developments have focused on the modi-
fication of the alkylidene moiety, and this approach has led to
new families of catalysts such as the indenylidene-containing
4
, but to the best of our knowledge, the catalytic performance
of these complexes in RCM has not been thoroughly investi-
gated.
Herein, we report the evaluation of the catalytic activity of
Phoban-containing ruthenium pre-catalysts in metathesis trans-
formations. First, a comparative study of complexes 4, 5, and
6
influence of the alkylidene moiety and Phoban ligand variations
on 1-octene metathesis activity has been investigated at different
temperatures and concentrations in the presence of these pre-
catalysts.
5
pre-catalysts 2a-c and isopropoxybenzylidene-containing phos-
6
phine-free complexes 3a,b (Figure 1). Thus, even if many
different ruthenium-based pre-catalysts have been synthesized
to date, little attention has been paid during this rapid develop-
ment to the tuning of phosphine ligands. In these systems, it
was long thought that only PCy3 (or tricyclopentylphosphines)
were viable ligands. Changing the phosphine affects phosphine
dissociation and rebinding to ruthenium and therefore has a
profound influence on the catalytic activity. By comparing the
dissociation from ruthenium of a series of substituted tri-
arylphosphines (PAr3) with tricyclohexylphosphine (PCy3),
Grubbs and co-workers7 showed that the faster phosphine
exchange was observed with PPh3. This effect was also observed
by Nolan and co-workers in their early studies on second-
9
1
2
in RCM reactions has been performed. Additionally, the
Results and Discussion
Ring-Closing Metathesis Experiments. To carry out a
thorough evaluation of pre-catalysts 4, 5 and 6, we tested their
catalytic activity in RCM involving different substrate types.
The results were compared to the ones obtained with reference
catalysts 1a and 2a. The benchmark substrates include variously
substituted and functionalized dienes and enynes. The reactions
were carried out with 2 mol % of catalyst, and reaction times
as well as temperatures have been optimized (Table 1).
As a general trend, pre-catalyst 4 exhibited a greater activity
for all tested substrates in this early study. The cyclization of
simple five- and six-membered ring substrates was achieved in
quantitative yields in less than 1 h (entries 1 and 4). Interestingly,
both trisubstituted olefins and enyne could be cyclized efficiently
in short reaction times (entries 2, 3, and 5). Similar results were
obtained with complexes 1a and 4 in the cyclization of
diallyldiethylmalonate 7. The examination of more challenging
substrates revealed a significantly higher activity of cyclohexy-
lphoban-containing pre-catalyst 4. For instance, compounds 9
and 11 were converted into the corresponding trisubstituted
olefins 10 and 12 in quantitative yields after 2 h using 4, while
4
generation systems. Nevertheless, this high lability and the lack
of bulkiness of PPh3 translated into a decreased stability of the
corresponding complex which is one of the reasons PCy3 is still
preferentially used. The choice of the ancillary ligand remains
a crucial parameter in finding the adequate compromise between
lability and stabilization. Phosphabicyclononane (Phoban) ligands,
8
initially developed in the 1960s, are interesting candidates for
developing active catalysts because they fulfill the requirements
of steric bulk and basicity for metathesis reactions.
The first synthesis of a Ru-Phoban complex was reported
9
in 2004 by Forman and co-workers (Figure 2). They employed
the relatively inexpensive 9-cyclohexyl-9-phospha-bicyclononane
as ligand for the synthesis of complex 4 and briefly evaluated
its efficacy in several metathesis reactions. The investigation
of self-metathesis (SM) and ethenolysis reactions of methyl
oleate catalyzed by complexes 4 and 5 showed interesting results
10
in terms of activity. Moreover, several calculations and
computational studies11 have been carried out examining catalyst
6
h were necessary to reach a complete conversion using
Grubbs’ catalyst 1a (entries 2 and 3). The formation of ether
4 was twice as fast using 4 when compared to 1a (entry 4).
(
5) (a) F u¨ rstner, A.; Grabowski, J.; Lehmann, C. W. J. Org. Chem. 1999,
1
6
4, 8275-8280. (b) Jafarpour, L.; Schanz, H.-J.; Stevens, E. D.; Nolan, S.
P. Organometallics 1999, 18, 5416-5419. (c) For a review on ruthenium
indenylidene complexes, see: Dragutan, V.; Dragutan, I.; Verpoort, F.
Platinum Metals ReV. 2005, 49, 33-40.
This difference of activity was also noticed in enyne ring-closing
metathesis (entry 5) because 16 was isolated after 2 h with 4
while the use of 1a in this reaction required 5 h to reach
completion. This difference of activity was previously com-
municated, and Chen mentioned that ligand symmetries and
conformational behavior could explain that kind of phenomenon.
However, by comparing indenylidene-containing pre-catalysts
5 and 6 with 2a, the superiority of Phoban- vs tricyclohexy-
lphosphine-containing complexes is not evident. Indeed, for all
(6) (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda,
A. H. J. Am. Chem. Soc. 1999, 121, 791-799. (b) Garber, S. B.; Kingsbury,
13
14
J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168-
8
179.
(7) Love, J. A.; Sanford, M. S.; Day, M. W.; Grubbs, R. H. J. Am. Chem.
Soc. 2003, 125, 10103-10109.
(
(
8) Mason, R. F.; van Winkle, J. L. U. S. Patent 3, 400, 163, 1968.
9) (a) Forman, G. S.; McConnell, A. E.; Tooze, R. P.; Dwyer, C. L.;
Serfontein, D. W. (Sasol Technology UK) World Patent ZA03/00087, 2003.
b) Forman, G. S.; McConnell, A. E.; Hanton, M. J.; Slawin, A. M. Z.;
(
Tooze, R. P.; Janse van Rensburg, W.; Meyer, W. H.; Dwyer, C.; Kirk, M.
(12) Sasol Technology UK and Umicore AG and Co KG, WO 2007/
010453 A2.
(13) Dwyer, C. L.; Kirk, M. M.; Meyer, W. H.; Janse van Rensburg,
W.; Forman, G. S. Organometallics 2006, 25, 3806-3812.
(14) Adlharh, C.; Chen, P. Angew. Chem., Int. Ed. 2002, 41, 4484-
4487.
M.; Serfontein, D. W. Organometallics 2004, 23, 4824-4827.
(10) Forman, G. S.; Bellabarba, R. M.; Tooze, R. P.; Slawin, A. M. Z.;
Karch, R.; Winde, R. J. Organomet. Chem. 2006, 691, 5513-5516.
11) Janse van Rensburg, W.; Steynberg, P. J.; Kirk, M. M.; Meyer, W.
H.; Forman, G. S. J. Organomet. Chem. 2006, 691, 5312-5325.
(
260 J. Org. Chem., Vol. 73, No. 1, 2008

Ru-Phoban Pre-Catalysts in Metathesis Reactions
TABLE 1. Comparison of Pre-Catalysts 1, 2a, 4, 5, and 6 in the
TABLE 2. Scope Extension for Pre-Catalysts 4 and 6a
a
RCM of Benchmark Substrates
a
Reactions performed in CH2Cl2 at rt using 2 mol % of pre-catalyst.
b
Reaction performed at 40 °C.
substrates described in Table 1, the catalytic activity of 2a
remains superior (entries 1-4) or at least equivalent (entry 5)
to 5. Moreover, an improvement of activity is only observed
for trisubstituted olefins with 6 (entries 2 and 3), while 2a
displays a higher activity for all other substrates tested (entries
1
, 4, and 5).
These observations confirm that it remains difficult to predict
the activity of a pre-catalyst in RCM because it is a highly
substrate-dependent reaction, and these further highlight the
differences between benzylidene- and indenylidene-containing
pre-catalysts. On the other hand, pre-catalysts 5 and 6 bearing
an indenylidene moiety were found to be efficient in mediating
the metathesis cyclization transformations of various substrates
in a few hours. Unfortunately, pre-catalyst 6 was not suitable
for the enyne metathesis reaction of 15 (entry 5). However, the
cyclizations of trisubstituted olefins using pre-catalyst 6 were
achieved under mild conditions and in short reaction times,
especially for malonate 9.
Overall, 9-isobutyl-9-phospha-bicyclononane-containing pre-
catalyst 6 gives better results than 9-cyclohexyl-9-phospha-
bicyclononane-containing complex 5 except for enyne 15. It is
important to note that the two different Phoban ligands are not
behaving in an analogous manner in RCM of trisubstituted
olefins because pre-catalyst 6 is the most active for this
application.
All these observations led us to investigate a wider range of
substrates using pre-catalyst 4 as well as pre-catalyst 6 that was
found to be particularly efficient in the RCM of trisubstituted
olefins. Special attention was focused on the influence of ring
size as well as the degree of substitution of the unsaturated bonds
and finally on functional group tolerance (Table 2).
Overall, the catalytic activity of pre-catalyst 4 proved to be
greater than that of 6. Several tosylamine-containing dienes were
used (entries 1-5). First, compounds 18 and 20 were isolated
a
Reactions performed in CH Cl at rt using 2 mol % of pre-catalyst.
2
2
b
c
Reaction performed in CH2Cl2 at 40 °C using 5 mol % of pre-catalyst.
Reaction performed at 40 °C.
in high yields with both pre-catalysts, but the use of 4 allowed
for a significant decrease of the reaction time when compared
to 6 (entries 1 and 2). Seven-membered ring product 22 was
isolated in quantitative yield after 1.5 h of reaction at room
temperature with pre-catalyst 4, while 6 required a longer
reaction time to reach completion. As expected, this type of
cyclization involves longer reaction times than for smaller rings.
The RCM of trisubstituted olefin 23 was achieved within 5.5
and 7.5 h, respectively, using complexes 4 and 6 (entry 4).
Despite the use of 5 mol % of catalyst loading, only low yields
were observed for tetrasubstituted olefin 26 (entry 5) even after
heating the reaction mixture at 40 °C for 24 h. Similar conditions
were applied for the cyclization of substrate 29, and no
conversion was observed. Seven-membered ring ether 32 was
isolated in good yield with both pre-catalysts but with a shorter
reaction time with the benzylidene complex (entry 8). RCM
reactions with substrates 33 and 39 (entries 9 and 12) particularly
emphasize the fact that 4 is more active than 6. Thus, thermal
activation was necessary to observe the formation of products
34 and 40 in the presence of 6, while complete conversions at
room temperature in relatively short times were observed with
J. Org. Chem, Vol. 73, No. 1, 2008 261

Boeda et al.
FIGURE 3. Conversion of 1-octene at 40 °C with pre-catalysts 4-6
25 ppm [Ru]). 9, 4; b, 5; 2, 6.
FIGURE 5. Conversion of 1-octene at 60 °C with pre-catalysts 4-6
(25 ppm [Ru]). 9, 4; b, 5; 2, 6.
(
TABLE 3. Final Conversions in 1-Octene Self-Metathesis after 24
h Using 25 ppm of [Ru]
a
entry
temperature (°C)
pre-catalyst
conversion (%)
4
5
6
4
5
6
4
5
6
61
64
50
63
63
37
55
48
30
1
40
2
50
60
3
a
Monitored by GC.
FIGURE 4. Conversion of 1-octene at 50 °C with pre-catalysts 4-6
25 ppm [Ru]). 9, 4; b, 5; 2, 6.
(
4. Finally, quantitative yields of 36 and 38 were obtained with
both pre-catalysts; however, reaction times were once again
shorter with 4 (entries 10 and 11).
Self-Metathesis of Terminal Alkenes. Self-metathesis rep-
resents an attractive reaction for the conversion of low value
feedstock into useful chemical products in the field of petro-
chemicals and polymers.15 In this context, the activity of pre-
catalysts 4-6 was first investigated in the self-metathesis
reaction of 1-octene for temperatures ranging from 40 to 60
°
1
C, at ruthenium metal concentrations of 25 ppm with a
-octene/Ru ratio of 27 000 (Figures 3-5). The initial reaction
rates increase in the order 6 < 5 < 4 above 40 °C, and 6 ≈ 5
FIGURE 6. Conversion of 1-octene at 50 °C with pre-catalysts 4-6
<
4 at 40 °C. However, similar conversions were reached with
and 5 after 24 h of reaction at all investigated temperatures
(
100 ppm [Ru]). 9, 4; b, 5; 2, 6.
4
1
6
(Table 3). These results indicate a slower initiation of the
Increasing the catalyst loading from 25 [Ru] to 100 ppm [Ru]
phenyl-indenylidene complex 5 compared to its benzylidene
analogue 4. Because after initiation, 5 and 4 both form the same
catalytic species with the same metathesis activity and decom-
position behavior, it is not surprising to obtain the same final
conversions.
When the reaction temperature was raised to 60 °C, lower
conversions were reached with 4 and 5 which indicate the
increasing decomposition of the active species at this temper-
ature. Concerning complex 6, such a stability effect was already
observed at 50 °C. The magnitude of the conversion decrease
indicates a lower stability of the isobutylphoban catalyst 6 as
compared to the cyclohexylphoban catalysts 5 and 4 (Table 3).
(Figure 6) results in a similar performance of complexes 5 and
6 with respect to conversion rate and final conversion in the
metathesis of 1-octene at 50 °C. It should be noted that higher
final conversions for 4 were previously obtained for 1-octene/
Ru ) 9000 when the catalyst was introduced as a solid, rather
1
7
than as a toluene solution.
Conclusions
To summarize, the use of complex 4 allows for the RCM of
dienes and enynes bearing various functionalities (tosylamides,
esters, ethers, and amides). This catalyst was found particularly
efficient in the RCM preparation of trisubstituted olefins, and
(
15) (a) Mol, J. C. Green Chem. 2002, 4, 5-13. (b) Mol, J. C. Top.
Catal. 2004, 27, 97-104.
16) Schwab, P.; Grubbs, R. H.; Ziller, Z. W. J. Am. Chem. Soc. 1996,
18, 100-110.
(17) Forman, G. S.; McConnell, A. E.; Tooze, R. P.; Janse van Rensburg,
W.; Meyer, W. H.; Kirk, M. M.; Dwyer, C. L.; Serfontein, D. W.
Organometallics 2005, 24, 4528-4542.
(
1
262 J. Org. Chem., Vol. 73, No. 1, 2008

Ru-Phoban Pre-Catalysts in Metathesis Reactions
a comparison between Grubbs’ catalyst and pre-catalyst 4
highlighted a significantly improved activity of the cyclohexy-
lphoban-containing complex. However, it should be noted that
General Procedure for the Self-Metathesis of 1-Octene. A
three-necked round-bottom flask (100 mL) equipped with a
condenser, an argon inlet, and a thermometer was charged with
1-octene (15 mL) and nonane (0.5 mL, internal standard) and heated
the limitation of this catalyst is apparent in tetrasubstituted olefin
formation that often represents a challenge.18 The superior
to the desired reaction temperature under argon. Stock solutions of
the respective catalysts in toluene were prepared before each
reaction. An amount of 4 mL of the stock solution was added to
the flask, and the reaction was stirred for 22 h. Samples (0.4 mL)
were withdrawn by syringe at regular time intervals, quenched with
a solution of toluene (0.5 mL) and tert-butyl-hydrogen peroxide (2
drops), and then analyzed by GC/FID. Conversions are reported
as the molar % of 1-octene that was converted to the desired
products, 7-tetradecene and ethylene.
performance of the cyclohexylphoban ligand over its isobutyl
counterpart for indenylidene-containing pre-catalysts was clearly
pointed out by studying 1-octene metathesis at a ruthenium
concentration of 25 ppm, whereas at 100 ppm, no difference is
apparent under the experimental conditions. The carbene moiety
(
4 vs 5) influenced catalyst initiation rather than achievable
conversion.
Experimental Section
Acknowledgment. We gratefully thank the ICIQ Foundation
for financial support. S.P.N. is an ICREA Research Professor.
Umicore AG is gratefully acknowledged for the generous gift
of pre-catalyst 6 and Cl2Ru(PCy3)2(3-phenylindenylidene). H.C.
acknowledges the Ministerio de Educaci o´ n y Ciencia (Spain)
for a postdoctoral fellowship.
General Procedure for RCM Reactions. A Schlenk flask was
filled under argon with the diene or the enyne (0.5 mmol) and DCM
(5 mL) before the addition of the pre-catalyst (0.01-0.025 mmol).
Progress of the reaction was monitored by TLC. The solvent was
removed under a vacuum, and the crude residue was purified by
flash column chromatography to yield the pure product.
Supporting Information Available: Compound characterization
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
(
18) (a) Berlin, J. M.; Campbell, K.; Ritter, T.; Funk, T. W.; Chlenov,
A.; Grubbs, R. H. Org. Lett. 2007, 9, 1339-1342. (b) Stewart, I. C.; Ung,
T.; Pletnev, A. A.; Berlin, J. M.; Grubbs, R. H.; Shrodi, Y. Org. Lett. 2007,
9
, 1589-1592.
JO702169P
J. Org. Chem, Vol. 73, No. 1, 2008 263